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Endocr Relat Cancer. 2015 Aug;22(4):545-59. doi: 10.1530/ERC-15-0029. Epub 2015 Jun 22.

Type 2 diabetes-related variants influence the risk of developing multiple myeloma: results from the IMMEnSE consortium.

Author information

1
Genomic Oncology AreaGENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS, Granada, 18016 Granada, SpainHematology DepartmentVirgen de las Nieves University Hospital, Granada, SpainGenomic Epidemiology GroupGerman Cancer Research Center (DKFZ), Heidelberg, GermanyDepartment of BiologyUniversity of Pisa, Pisa, ItalyDepartment of HematologyHospital Universitario Doce de Octubre, Madrid, SpainArea of Genomic MedicineGENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, SpainSemmelweis UniversityBudapest, HungaryHaematology DepartmentUniversity Hospital of Salamanca and IBSAL, Salamanca, SpainMedical University of LodzLodz, PolandINSERM UMR 1052/CNRS 5286Université Claude Bernard Lyon I, Lyon, FranceMorales Meseguer General University HospitalMurcia, SpainHaematoloy ClinikHolly Cross Cancer Center, Kielce, PolandINSERMU900, Genetic Epidemiology of Cancers team, Institut Curie, Mines ParisTech, Paris, FranceLife and Health Sciences Research Institute (ICVS)School of Health Sciences, University of Minho, Braga, PortugalICVS/3B's - PT Government Associate LaboratoryBraga/Guimarães, PortugalMolecular Oncology Research CenterBarretos Cancer Hospital, Barretos, BrazilIDIBELL - Catalan Institute of OncologyUniversity of Barcelona, Barcelona 08907, SpainDepartment of HematologyCracow University Hospital, Cracow, PolandOrgan CenterHospital of Southern Jutland, DK-6200 Aabenraa, DenmarkFaculty of Health SciencesInstitute of Regional Health Research, University of Southern Denmark, DK-5000 Odense C, DenmarkUO HematologyDepartment of Internal and Experimental Medicine, University of Pisa, Pisa, ItalyClinic of Biochemistry and ImmunologyLaboratory Center, Hospital of Southern Jutland, Aabenraa, DenmarkDepartment of HaematologyRigshospitalet and Roskilde Hospital, Copenhagen University, Copenhagen, Denmark Genomic Oncology AreaGENYO, Cen
2
Genomic Oncology AreaGENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS, Granada, 18016 Granada, SpainHematology DepartmentVirgen de las Nieves University Hospital, Granada, SpainGenomic Epidemiology GroupGerman Cancer Research Center (DKFZ), Heidelberg, GermanyDepartment of BiologyUniversity of Pisa, Pisa, ItalyDepartment of HematologyHospital Universitario Doce de Octubre, Madrid, SpainArea of Genomic MedicineGENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, SpainSemmelweis UniversityBudapest, HungaryHaematology DepartmentUniversity Hospital of Salamanca and IBSAL, Salamanca, SpainMedical University of LodzLodz, PolandINSERM UMR 1052/CNRS 5286Université Claude Bernard Lyon I, Lyon, FranceMorales Meseguer General University HospitalMurcia, SpainHaematoloy ClinikHolly Cross Cancer Center, Kielce, PolandINSERMU900, Genetic Epidemiology of Cancers team, Institut Curie, Mines ParisTech, Paris, FranceLife and Health Sciences Research Institute (ICVS)School of Health Sciences, University of Minho, Braga, PortugalICVS/3B's - PT Government Associate LaboratoryBraga/Guimarães, PortugalMolecular Oncology Research CenterBarretos Cancer Hospital, Barretos, BrazilIDIBELL - Catalan Institute of OncologyUniversity of Barcelona, Barcelona 08907, SpainDepartment of HematologyCracow University Hospital, Cracow, PolandOrgan CenterHospital of Southern Jutland, DK-6200 Aabenraa, DenmarkFaculty of Health SciencesInstitute of Regional Health Research, University of Southern Denmark, DK-5000 Odense C, DenmarkUO HematologyDepartment of Internal and Experimental Medicine, University of Pisa, Pisa, ItalyClinic of Biochemistry and ImmunologyLaboratory Center, Hospital of Southern Jutland, Aabenraa, DenmarkDepartment of HaematologyRigshospitalet and Roskilde Hospital, Copenhagen University, Copenhagen, Denmark.

Abstract

Type 2 diabetes (T2D) has been suggested to be a risk factor for multiple myeloma (MM), but the relationship between the two traits is still not well understood. The aims of this study were to evaluate whether 58 genome-wide-association-studies (GWAS)-identified common variants for T2D influence the risk of developing MM and to determine whether predictive models built with these variants might help to predict the disease risk. We conducted a case-control study including 1420 MM patients and 1858 controls ascertained through the International Multiple Myeloma (IMMEnSE) consortium. Subjects carrying the KCNQ1rs2237892T allele or the CDKN2A-2Brs2383208G/G, IGF1rs35767T/T and MADDrs7944584T/T genotypes had a significantly increased risk of MM (odds ratio (OR)=1.32-2.13) whereas those carrying the KCNJ11rs5215C, KCNJ11rs5219T and THADArs7578597C alleles or the FTOrs8050136A/A and LTArs1041981C/C genotypes showed a significantly decreased risk of developing the disease (OR=0.76-0.85). Interestingly, a prediction model including those T2D-related variants associated with the risk of MM showed a significantly improved discriminatory ability to predict the disease when compared to a model without genetic information (area under the curve (AUC)=0.645 vs AUC=0.629; P=4.05×10(-) (06)). A gender-stratified analysis also revealed a significant gender effect modification for ADAM30rs2641348 and NOTCH2rs10923931 variants (Pinteraction=0.001 and 0.0004, respectively). Men carrying the ADAM30rs2641348C and NOTCH2rs10923931T alleles had a significantly decreased risk of MM whereas an opposite but not significant effect was observed in women (ORM=0.71 and ORM=0.66 vs ORW=1.22 and ORW=1.15, respectively). These results suggest that TD2-related variants may influence the risk of developing MM and their genotyping might help to improve MM risk prediction models.

KEYWORDS:

diabetes; genetic variants; multiple myeloma; susceptibility

PMID:
26099684
DOI:
10.1530/ERC-15-0029
[Indexed for MEDLINE]

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